Background and Purpose: Diminished vasoreactivity (VR) has been evidenced in patients with hemispheric small vessel disease, however, there is no data regarding vertebrobasilar (VB) territory VR changes in patients with subcortical vascular encephalopathy located in the brainstem. Therefore, we compared the cerebral blood flow velocity (CBFV) responses of the VB system during different vasoregulatory challenges in healthy volunteers to those in patients with brainstem lacunar infarcts. Methods: In 20 patients with brainstem lacunar infarcts and in 10 healthy volunteers the VR of the VB system was measured by analyzing the CBFV changes during different stimulation paradigms (ventilation, tilting and acetazolamide tests). During transcranial Doppler registration the systemic blood pressure and the expiratory partial CO<sub>2</sub> pressure were monitored. Results: During hypercapnia the VR was significantly higher in the control group than in the patient group (10.1 ± 4.9 vs. 3.4 ± 5.0 cm/s/kPa, p = 0.0025). In a subgroup of patients with mean baseline CBFV <25 cm/s the VR was 1.5 ± 2.4 cm/ s/kPa, while patients with mean baseline CBFV >25 cm/s showed a significantly higher value (7.8 ± 6.9 cm/s/kPa). Furthermore, in patients with mean baseline CBFV <25 cm/s the pulsatility index was significantly higher than in patients with mean baseline CBFV >25 cm/s (1.11 ± 0.26 vs. 0.86 ± 0.19, p = 0.0325), reflecting significantly higher vascular resistance in the former group. Although CBFV measurements during tilting and acetazolamide tests tended to support these findings, they showed no significant differences between patients and controls. Conclusion: Patients with cerebral microangiopathy involving the brainstem showed impaired VR in the VB flow territory in association with baseline CBFV.